Primary Malignant Brain TumorPhase 1NCT05892653
A Study of ABM-1310 in Patients With BRAF V600-Mutant Relapsed and Drug Resistant Primary Malignant Brain Tumors
A Phase 1 study testing ABM-1310 in people with Primary Malignant Brain Tumor, run by ABM Therapeutics Shanghai Company Limited at 4 sites in China.
Trial summary
Overall Design: This is a phase I, open-label, multicenter clinical study to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-cancer efficacy of ABM-1310 in patients with BRAF V600-mutant relapsed and drug resistant primary malignant brain tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Malignant Brain Tumor
- What is being tested?
- ABM-1310
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 4 sitesChina
- Study dates
- 30 Jun 2023to 27 Aug 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects who are able to understand and voluntarily sign informed consent forms (ICFs).
- Male and female subjects at the age of ≥18 at the time of screening.
- Patients with histologically or cytologically-confirmed, primary malignant brain tumor with (a) failure of prior standard therapy, (b) no standard therapy available, or (c) for whom standard therapy is not applicable considered by the patient or treating physician, or (d) intolerance to standard treatment. Subjects who were previously treated with BRAF and/or MEK inhibitors are allowed to be enrolled in this study.
- Documentation of positive BRAF V600 mutation is required for enrollment. It is recommended to provide sufficient fresh/archived tumor tissue samples (formalin-fixed paraffin-embedded tumor specimens [preferred]) or 5-10 available unstained sections of good quality for verification of BRAF V600 mutation status at the central laboratory. For any subject who is unable to provide suitable and adequate tumor specimens, re-biopsy (with controllable safety) can be performed in a non-mandatory manner if it is feasible as assessed by the investigator and the subject gives informed consent; if re-biopsy is impossible or refused by the subject, his/her eligibility for enrollment shall be confirmed by both the investigator and the sponsor.
- Patients with primary malignant brain tumors that are asymptomatic, or that are symptomatic but on a stable or decreasing dose of steroids for at least 2 weeks are eligible for enrollment. The specific criteria are as follows:Subjects with inactive and asymptomatic primary malignant brain tumors;Subjects who have active, mild neurological signs and symptoms currently requiring no therapy with steroids, and have no history of epileptic seizure within 2 weeks prior to initiation of treatment;Subjects who have active, neurological signs and symptoms and were on a stable or gradually reducing dose up to 5 mg of dexamethasone (or equivalent) per day within 2 weeks prior to initiation of treatment;
- Antitumor efficacy was evaluated using the RANO criteria, which required the presence of at least one measurable lesion (the diameters that are perpendicular to each other are not less than 10 mm). Lesions previously treated with radiotherapy shall not be deemed as target lesions unless significant progression as shown on imaging.
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- Karnofsky PS score of ≥ 60.
- Survival expectancy ≥ 3 months.
- Adequate organ function (no blood transfusion and no use of granulocyte colony-stimulating factor, or other hematopoietic stimulator support within 2 weeks before the first administration of the study drug) confirmed as evidenced by:Absolute Neutrophil Count (ANC) ≥ 1.5×10^9/L;Hemoglobin (Hgb) ≥ 90 g/dl;Platelets (Plt) ≥ 75×10^9/L;AST/ALT ≤ 2.5 x ULN or ≤ 5.0 x ULN if liver metastases are present;Bilirubin total ≤ 1.5 x ULN, or bilirubin direct < ULN for patients with bilirubin total levels >1.5 ULN;Serum creatinine < 1.5 x ULN or creatinine clearance > 50 mL/min (as calculated via Cockcroft-Gault formula based on the actual body weight of the subject;International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 x ULN for subjects not receiving anticoagulant therapy, and INR is maintained within the standard range of treatment prior to starting study drug for subjects receiving anticoagulant therapy.
- Hepatitis B virus surface antigen (HBsAg) is negative, or HBsAg is positive but HBV DNA titer is below the lower limit of positive detection of the participating site at screening.HBsAg-positive or HBV-DNA positive subjects shall be managed according to institutional guidelines (anti-HBV therapy, where appropriate, and close monitoring of liver function and HBV-DNA replication shall be performed).
- Negative hepatitis C virus (HCV) antibody test or positive HCV antibody test at the time of screening followed by a negative HCV-RNA test result.HCV-RNA testing is performed only for subjects with a positive HCV antibody test result.
- Negative HIV test result at the time of screening.
- All pre-menopausal women and women with menolipsis < 12 months should have a negative pregnancy test result within 7 days before starting study treatment.
- Must agree to take sufficient contraceptive methods before initiation of study treatment, during the study, and for at least 3 months after the last dose of the study drug.
- Subjects who are able to swallow a capsule in whole (without chewing, crushing, or opening).
Who cannot join
- Women who are pregnant or breast-feeding.
- Subjects with history of neoplasm malignant (except for primary malignant brain tumors) within 5 years prior to screening, excluding cured carcinoma in situ of cervix, non-melanoma skin cancer, localized prostate cancer and other tumors/cancers that have undergone radical treatment and shown no signs of disease for at least 3 years (This exclusion criterion is only applicable for dose expansion stage). For the dose escalation stage, any patient with double primary malignant solid tumors who can indeed benefit from this study as confirmed by the investigator is eligible for the screening.
- Subjects with intracranial hypertension or associated risks (e.g., intracranial infection, intracranial hemorrhage) to be controlled.
- Subjects with clinically uncontrolled pleural effusion, pericardial effusion, or ascites who, in the judgement of the investigator, are not eligible for enrollment.
- Subjects with history of symptomatic stroke within 6 months prior to initiation of study treatment.
- Subjects with epileptic seizure within 14 days prior to initiation of study treatment.
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- Impaired cardiac function or clinically significant cardiovascular disorder, including but not limited to any of the following:Left Ventricular Ejection Fraction (LVEF) < 50% as determined via cardiac ultrasound.Long QT syndrome congenital.QTcF (as corrected via Fridericia formula) ≥ 450 ms at screening.Second-degree type II AV block or third-degree AV block.Unstable angina pectoris within 6 months prior to starting study drug.Acute myocardial infarction within 6 months prior to starting study drug.New York Heart Association (NYHA) Class II or higher heart failure within 6 months prior to study treatment.Ventricular arrhythmias > Grade 2 within 6 months prior to study treatment.Poorly controlled hypertension as defined as systolic blood pressure of >160 mmHg or diastolic blood pressure of > 100 mmHg despite use of antihypertensive medications.Combined with any pulmonary embolism, or presence of any serious deep vein thrombosis on lower extremities that require medical interventions such as vena cava filter insertion at the screening.
- Poorly controlled diabetes (fasting glucose > 10 mmol/L or Glycosylated Haemoglobin (HbA1c) > 8%) despite standard drug therapy.
- Subjects with:CTCAE grade 2 or higher unresolved diarrhea, or Impaired gastrointestinal (GI) function or GI diseases that may significantly alter the absorption of ABM-1310 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
- Previous or current, Grade 2 or higher eye disorder, such as retinal vein occlusion (RVO).
- Severe chronic or active infections requiring intravenous anti-infective therapy within 2 weeks prior to study treatment, including but not limited infectious complications leading to hospitalization, bacteremia, severe pneumonia, or active tuberculosis.Subjects with local fungal infections of skin or nails are allowed for enrollment. Subjects receiving prophylactic antibiotics (e.g., to prevent urinary tract infections or exacerbations of chronic obstructive pulmonary disease) are eligible for study (except for antibiotics prohibited by the protocol).
- Subjects with solid organ or hematopoietic stem cell transplant within the past 5 years.
- Patients receiving chemotherapy, targeted therapy, or immunotherapy within 4 weeks prior to study treatment, including the followings:Receiving nitrosourea or mitomycin-C within 6 weeks prior to study treatment.Receiving fluorouracil or small molecule targeted drug therapy within 5 half-lives or 2 weeks (whichever is longer) prior to study treatment.Receiving Chinese herbal or patent medicine within 2 weeks prior to study treatment for anti-tumor indications.
- Patients receiving radiotherapy to head within 4 weeks prior to study treatment.
- Adverse reactions resulted from prior antitumor therapy that have not resolved to baseline or ≤ grade 1 (CTCAE 5.0) , except alopecia or ≤ grade 2 peripheral neuropathy, hypothyroidism stabilized by hormone replacement therapy, etc.
- Subjects who have undergone major surgery within 4 weeks prior to study treatment or who have not recovered from side effects of such therapy or who are expected to undergo major surgery during study treatment. However, a minimum of 2 weeks recovery time from major surgery to starting study drug is required if in investigator's opinion the patient has recovered from such major surgery.
- Subjects currently receiving therapeutic doses of warfarin sodium or any other coumarin-derivative anticoagulants.
- Subjects who are currently receiving treatment with medication that has a known risk to prolong the QT interval and cannot either be discontinued or switched to a different medication prior to starting study drug.
- Known, documented or suspected history of drug abuse, expect opioids prescribed for pain relief, etc.
- Past or current evidence of any condition, therapy, or laboratory abnormality that, in the opinion of the investigator, might affect the results of the study, and interfere with the subject's participation and study compliance.
- Other severe and/or uncontrolled concomitant diseases that could cause unacceptable safety risks or compromise compliance with the study protocol.
- Other conditions that, in the judgement of the investigator, are inappropriate for enrollment in the study.
Trial locations and contacts
4 sites in 1 country.
China4 sites
Beijing Tiantan Hospital Affiliated to Capital Medical University
Beijing, Beijing Municipality, 100070
Huashan Hospital Affiliated to Fudan University
Shanghai, Shanghai Municipality, 200040
Shenzhen Second People's Hospital
Shenzhen, Guangdong, 518020
First affiliated hospital to SuZhou University
Suzhou, Jiangsu, 215006
About this study
Official title: A Phase I, Open-Label, Multicenter Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics &Preliminary Anti-Cancer Efficacy of ABM-1310 in Patients With BRAF V600-Mutant Relapsed &Drug Resistant Primary Malignant Brain Tumors
Overall Design: This is a phase I, open-label, multicenter clinical study to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-cancer efficacy of ABM-1310 in patients with BRAF V600-mutant relapsed and drug resistant primary malignant brain tumors.
The study including four periods of screening (28 days), treatment (no more than 2 years), safety follow-up and survival follow-up.
Read more
This study consists of two stages: dose escalation and dose expansion. During the dose escalation stage, a classic "3+3" design will be used to guide dose escalation to determine MTD and RP2D. Three to six subjects are expected to be enrolled in each dose group and at least 6 subjects are enrolled in the MTD/highest dose group. The total number of subjects enrolled during the dose escalation stage will depend on the amount of DLT and the total number of dose levels explored. If DLT is not observed in the first 3 subjects enrolled for each dose level, the Safety Monitoring Committee (SMC, including investigators, pharmacologists, and the sponsor's medical specialists, and other experienced members specially invited as necessary) will review the cumulative safety data of subjects at each dose level and decide whether to proceed with dose escalation upon the completion of study treatment at least for the DLT evaluation period (28 days of Cycle 1).
The dose expansion stage in this study will be initiated at the MTD or the optimal dose determined by the SMC as a fixed dose level (MTD or the optimal dose needs to be reviewed by the SMC and subjects are safe and tolerable at that dose level). The dose expansion stage is expected to include the following two cohorts of relapsed and drug resistant primary malignant brain tumors with BRAF V600 mutations:Cohort 1: GBM, N = up to 25 patients; Cohort 2: In addition to GBM, other primary malignant brain tumors, N = up to 15 patients.
In this study, the corresponding sample size for each cohort/tumor type may be determined according to the actual efficacy and safety data obtained. After each cohort included the first 10 patients, the available safety, efficacy, and PK data were analyzed. Based on the analysis results, the sponsor decided whether to continue recruiting patients for the study.
- Conditions
- Primary Malignant Brain Tumor
- Being tested
- ABM-1310
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ABM-1310Drug
Dose Escalation Stage: Subjects will be given oral dosing of ABM-1310 twice daily (BID) for 28-day cycles of continuous administration until progressive disease (PD), unacceptable toxicity, or other withdrawal criteria are met as clinically observed.
Dose Expansion Stage: Subjects will begin to receive oral doses of ABM-1310, BID, for 28-day cycles at a fixed dose level (as determined at the dose escalation stage) until PD, unacceptable toxicity, or other withdrawal criteria are met as clinically observed.
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation and Dose Expansion | Experimental | During the dose escalation stage, a classic "3+3" design will be used to guide dose escalation to determine MTD and RP2D. Three to six subjects are expected to be enrolled in each dose group and at least 6 subjects are enrolled in the MTD/highest dose group. The total number of subjects enrolled during the dose escalation stage will depend on the amount of DLT and the total number of dose levels explored. If DLT is not observed in the first 3 subjects enrolled for each dose level, the Safety Monitoring Committee (SMC) will review the cumulative safety data of subjects at each dose level and decide whether to proceed with dose escalation upon the completion of study treatment at least for the DLT evaluation period (28 days of Cycle 1). The dose expansion stage in this study will be initiated at the MTD or the optimal dose determined by the SMC as a fixed dose level (MTD or the optimal dose needs to be reviewed by the SMC and subjects are safe and tolerable at that dose level). Receives: Drug: ABM-1310 |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD
MTD is defined as the highest dose level at which DLT is observed in ≤ 1/6 subjects at one single dose group.
Measured: From the enrollment of subjects to the end of Cycle 1 (each cycle is 28 days) or up to treatment discontinuation, whichever occurs first, assessed up to 28 days.
Recommended Phase 2 Dose(PR2D)
RP2D will be a dose either below or equal to MTD
Measured: From the enrollment of subjects to the end of Cycle 1 (each cycle is 28 days) or up to treatment discontinuation, whichever occurs first, assessed up to 28 days.
Dose Limiting Toxicity(DLT)
DLT will be evaluated according to NCI-CTCAE V5.0 criteria
Measured: cycle 1（28 days）
The incidence of treatment-related adverse events AE(s)
Safety and tolerability of ABM-1310 monotherapy
Measured: Up to 28 days from treatment discontinuation
Number of participants with abnormal laboratory values
Safety and tolerability of ABM-1310 monotherapy
Measured: Up to 28 days from treatment discontinuation
Number of participants with abnormal vital signs
Safety and tolerability of ABM-1310 monotherapy
Measured: Up to 28 days from treatment discontinuation
Number of participants with abnormal physical examinations
Safety and tolerability of ABM-1310 monotherapy
Measured: Up to 28 days from treatment discontinuation
Number of participants with abnormal ophthalmic evaluation
Safety and tolerability of ABM-1310 monotherapy
Measured: Up to 28 days from treatment discontinuation
Number of participants with abnormal ECG
Safety and tolerability of ABM-1310 monotherapy
Measured: Up to 28 days from treatment discontinuation
Number of participants with abnormal Karnofsky PS
Safety and tolerability of ABM-1310 monotherapy
Measured: Up to 28 days from treatment discontinuation
Secondary outcomes (10)
Objective Response Rate (ORR)
Preliminary efficacy of ABM-1310 monotherapy
Measured: From the enrollment of subjects to the time of disease progression in radiological imaging or death from any cause, whichever occurs first, assessed approximately 12 months.
Disease Control Rate(DCR)
Preliminary efficacy of ABM-1310 monotherapy
Measured: From the enrollment of subjects to the time of disease progression in radiological imaging or death from any cause, whichever occurs first, assessed approximately 12 months.
Duration of Response（DOR）
Preliminary efficacy of ABM-1310 monotherapy
Measured: From the enrollment of subjects to the time of disease progression in radiological imaging or death from any cause, whichever occurs first, assessed approximately 12 months.
Progression free survival (PFS)
Preliminary efficacy of ABM-1310 monotherapy
Measured: From the enrollment of subjects to the time of disease progression in radiological imaging or death from any cause, whichever occurs first, assessed approximately 12 months.
Overall Survival(OS)
Preliminary efficacy of ABM-1310 monotherapy
Measured: From the enrollment of subjects to the time of death from any cause or the study discontinuation, whichever occurs first, assessed approximately 18 months.
Peak Concentration（Cmax）
Pharmacokinetic (PK) profile of ABM-1310 monotherapy
Measured: 12 hours after the first dose on the first day of cycle 1 (each cycle is 28 days)
Time to Cmax(Tmax)
Pharmacokinetic (PK) profile of ABM-1310 monotherapy
Measured: 12 hours after the first dose on the first day of cycle 1 (each cycle is 28 days)
AUC from time 0 to the time of last measurable concentration（AUC0-last)
Pharmacokinetic (PK) profile of ABM-1310 monotherapy
Measured: Up to Day 2, Day 8, Day 15, Day 22 and Day 28 of Cycle 1. Up to Day 1 and Day 2 of Cycle2. After Cycle2, tests every 2 cycles (each cycle is 28 days)
Steady-state Concentration（Css）
PK characteristics of repeated administration of ABM-1310 monotherapy
Measured: At the Day 1 and Day 2 of Cycle 2 (each cycle is 28 days)
Terminal half-life（T1/2）
Pharmacokinetic (PK) profile of ABM-1310 monotherapy
Measured: 12 hours after the first dose on the first day of cycle 1 (each cycle is 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2023
- Study start30 Jun 2023
- Primary completion27 Aug 2024
- Study completion27 Aug 2024
Why it stopped: Adjustment of the applicant's research and development strategy
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Malignant Brain TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- ABM Therapeutics Shanghai Company Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Wenbin Li, Principal investigator, Beijing Tiantan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05892653
- Sponsor's protocol ID
- ABM1310X1102C
- Status last verified
- Nov 2024
- First submitted
- 18 May 2023
- Last updated
- 29 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open-Label, Multicenter Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics &Preliminary Anti-Cancer Efficacy of ABM-1310 in Patients With BRAF V600-Mutant Relapsed &Drug Resistant Primary Malignant Brain Tumors
- ClinicalTrials.gov ID
- NCT05892653
- Acronym / sponsor ID
- ABM1310X1102C
- Conditions
- Primary Malignant Brain Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Adjustment of the applicant's research and development strategy
- Enrolment
- 15 participants (actual)
- Lead sponsor
- ABM Therapeutics Shanghai Company LimitedIndustry (pharma, biotech, devices)
- Study start
- 30 Jun 2023 (actual)
- Primary completion
- 27 Aug 2024 (actual)
- Study completion
- 27 Aug 2024 (actual)
- First posted
- 7 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Overall Design: This is a phase I, open-label, multicenter clinical study to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-cancer efficacy of ABM-1310 in patients with BRAF V600-mutant relapsed and drug resistant primary malignant brain tumors.
The study including four periods of screening (28 days), treatment (no more than 2 years), safety follow-up and survival follow-up.
This study consists of two stages: dose escalation and dose expansion. During the dose escalation stage, a classic "3+3" design will be used to guide dose escalation to determine MTD and RP2D. Three to six subjects are expected to be enrolled in each dose group and at least 6 subjects are enrolled in the MTD/highest dose group. The total number of subjects enrolled during the dose escalation stage will depend on the amount of DLT and the total number of dose levels explored. If DLT is not observed in the first 3 subjects enrolled for each dose level, the Safety Monitoring Committee (SMC, including investigators, pharmacologists, and the sponsor's medical specialists, and other experienced members specially invited as necessary) will review the cumulative safety data of subjects at each dose level and decide whether to proceed with dose escalation upon the completion of study treatment at least for the DLT evaluation period (28 days of Cycle 1).
The dose expansion stage in this study will be initiated at the MTD or the optimal dose determined by the SMC as a fixed dose level (MTD or the optimal dose needs to be reviewed by the SMC and subjects are safe and tolerable at that dose level). The dose expansion stage is expected to include the following two cohorts of relapsed and drug resistant primary malignant brain tumors with BRAF V600 mutations:Cohort 1: GBM, N = up to 25 patients; Cohort 2: In addition to GBM, other primary malignant brain tumors, N = up to 15 patients.
In this study, the corresponding sample size for each cohort/tumor type may be determined according to the actual efficacy and safety data obtained. After each cohort included the first 10 patients, the available safety, efficacy, and PK data were analyzed. Based on the analysis results, the sponsor decided whether to continue recruiting patients for the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation and Dose Expansion | Experimental | Drug: ABM-1310During the dose escalation stage, a classic "3+3" design will be used to guide dose escalation to determine MTD and RP2D. Three to six subjects are expected to be enrolled in each dose group and at least 6 subjects are enrolled in the MTD/highest dose group. The total number of subjects enrolled during the dose escalation stage will depend on the amount of DLT and the total number of dose levels explored. If DLT is not observed in the first 3 subjects enrolled for each dose level, the Safety Monitoring Committee (SMC) will review the cumulative safety data of subjects at each dose level and decide whether to proceed with dose escalation upon the completion of study treatment at least for the DLT evaluation period (28 days of Cycle 1). The dose expansion stage in this study will be initiated at the MTD or the optimal dose determined by the SMC as a fixed dose level (MTD or the optimal dose needs to be reviewed by the SMC and subjects are safe and tolerable at that dose level). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Subjects who are able to understand and voluntarily sign informed consent forms (ICFs).
- Male and female subjects at the age of ≥18 at the time of screening.
- Patients with histologically or cytologically-confirmed, primary malignant brain tumor with (a) failure of prior standard therapy, (b) no standard therapy available, or (c) for whom standard therapy is not applicable considered by the patient or treating physician, or (d) intolerance to standard treatment. Subjects who were previously treated with BRAF and/or MEK inhibitors are allowed to be enrolled in this study.
- Documentation of positive BRAF V600 mutation is required for enrollment. It is recommended to provide sufficient fresh/archived tumor tissue samples (formalin-fixed paraffin-embedded tumor specimens [preferred]) or 5-10 available unstained sections of good quality for verification of BRAF V600 mutation status at the central laboratory. For any subject who is unable to provide suitable and adequate tumor specimens, re-biopsy (with controllable safety) can be performed in a non-mandatory manner if it is feasible as assessed by the investigator and the subject gives informed consent; if re-biopsy is impossible or refused by the subject, his/her eligibility for enrollment shall be confirmed by both the investigator and the sponsor.
- Patients with primary malignant brain tumors that are asymptomatic, or that are symptomatic but on a stable or decreasing dose of steroids for at least 2 weeks are eligible for enrollment. The specific criteria are as follows:Subjects with inactive and asymptomatic primary malignant brain tumors;Subjects who have active, mild neurological signs and symptoms currently requiring no therapy with steroids, and have no history of epileptic seizure within 2 weeks prior to initiation of treatment;Subjects who have active, neurological signs and symptoms and were on a stable or gradually reducing dose up to 5 mg of dexamethasone (or equivalent) per day within 2 weeks prior to initiation of treatment;
Key exclusion criteria (22 listed)
- Women who are pregnant or breast-feeding.
- Subjects with history of neoplasm malignant (except for primary malignant brain tumors) within 5 years prior to screening, excluding cured carcinoma in situ of cervix, non-melanoma skin cancer, localized prostate cancer and other tumors/cancers that have undergone radical treatment and shown no signs of disease for at least 3 years (This exclusion criterion is only applicable for dose expansion stage). For the dose escalation stage, any patient with double primary malignant solid tumors who can indeed benefit from this study as confirmed by the investigator is eligible for the screening.
- Subjects with intracranial hypertension or associated risks (e.g., intracranial infection, intracranial hemorrhage) to be controlled.
- Subjects with clinically uncontrolled pleural effusion, pericardial effusion, or ascites who, in the judgement of the investigator, are not eligible for enrollment.
- Subjects with history of symptomatic stroke within 6 months prior to initiation of study treatment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ABM-1310Dose Escalation Stage: Subjects will be given oral dosing of ABM-1310 twice daily (BID) for 28-day cycles of continuous administration until progressive disease (PD), unacceptable toxicity, or other withdrawal criteria are met as clinically observed. Dose Expansion Stage: Subjects will begin to receive oral doses of ABM-1310, BID, for 28-day cycles at a fixed dose level (as determined at the dose escalation stage) until PD, unacceptable toxicity, or other withdrawal criteria are met as clinically observed. | Drug | Dose Escalation and Dose Expansion |
Primary outcome
MTD
Time frame: From the enrollment of subjects to the end of Cycle 1 (each cycle is 28 days) or up to treatment discontinuation, whichever occurs first, assessed up to 28 days.
MTD is defined as the highest dose level at which DLT is observed in ≤ 1/6 subjects at one single dose group.
Recommended Phase 2 Dose(PR2D)
Time frame: From the enrollment of subjects to the end of Cycle 1 (each cycle is 28 days) or up to treatment discontinuation, whichever occurs first, assessed up to 28 days.
RP2D will be a dose either below or equal to MTD
Dose Limiting Toxicity(DLT)
Time frame: cycle 1（28 days）
DLT will be evaluated according to NCI-CTCAE V5.0 criteria
The incidence of treatment-related adverse events AE(s)
Time frame: Up to 28 days from treatment discontinuation
Safety and tolerability of ABM-1310 monotherapy
Number of participants with abnormal laboratory values
Time frame: Up to 28 days from treatment discontinuation
Safety and tolerability of ABM-1310 monotherapy
Number of participants with abnormal vital signs
Time frame: Up to 28 days from treatment discontinuation
Safety and tolerability of ABM-1310 monotherapy
Number of participants with abnormal physical examinations
Time frame: Up to 28 days from treatment discontinuation
Safety and tolerability of ABM-1310 monotherapy
Number of participants with abnormal ophthalmic evaluation
Time frame: Up to 28 days from treatment discontinuation
Safety and tolerability of ABM-1310 monotherapy
Number of participants with abnormal ECG
Time frame: Up to 28 days from treatment discontinuation
Safety and tolerability of ABM-1310 monotherapy
Number of participants with abnormal Karnofsky PS
Time frame: Up to 28 days from treatment discontinuation
Safety and tolerability of ABM-1310 monotherapy
10 secondary outcomes
Objective Response Rate (ORR)
Time frame: From the enrollment of subjects to the time of disease progression in radiological imaging or death from any cause, whichever occurs first, assessed approximately 12 months.
Disease Control Rate(DCR)
Time frame: From the enrollment of subjects to the time of disease progression in radiological imaging or death from any cause, whichever occurs first, assessed approximately 12 months.
Duration of Response（DOR）
Time frame: From the enrollment of subjects to the time of disease progression in radiological imaging or death from any cause, whichever occurs first, assessed approximately 12 months.
Progression free survival (PFS)
Time frame: From the enrollment of subjects to the time of disease progression in radiological imaging or death from any cause, whichever occurs first, assessed approximately 12 months.
Overall Survival(OS)
Time frame: From the enrollment of subjects to the time of death from any cause or the study discontinuation, whichever occurs first, assessed approximately 18 months.
Peak Concentration（Cmax）
Time frame: 12 hours after the first dose on the first day of cycle 1 (each cycle is 28 days)
Time to Cmax(Tmax)
Time frame: 12 hours after the first dose on the first day of cycle 1 (each cycle is 28 days)
AUC from time 0 to the time of last measurable concentration（AUC0-last)
Time frame: Up to Day 2, Day 8, Day 15, Day 22 and Day 28 of Cycle 1. Up to Day 1 and Day 2 of Cycle2. After Cycle2, tests every 2 cycles (each cycle is 28 days)
Steady-state Concentration（Css）
Time frame: At the Day 1 and Day 2 of Cycle 2 (each cycle is 28 days)
Terminal half-life（T1/2）
Time frame: 12 hours after the first dose on the first day of cycle 1 (each cycle is 28 days)
Results and safety
The study was stopped early (reason given: Adjustment of the applicant's research and development strategy). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2024.
- Individual participant dataSharing planned: No
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Ependymoma, Medulloblastoma
Not yet recruitingObservational study
Evaluating Biomarkers of Cognitive Dysfunction in Patients With Cancer
Brain Tumor Adult, Brain Metastases From Solid Tumors
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wenbin Li principal investigator
Beijing Tiantan Hospital
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ABM-1310 in people with Primary Malignant Brain Tumor, run by ABM Therapeutics Shanghai Company Limited at 4 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 29 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Adjustment of the applicant's research and development strategy). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MTD (time frame: From the enrollment of subjects to the end of Cycle 1 (each cycle is 28 days) or up to treatment discontinuation, whichever occurs first, assessed up to 28 days.). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2024.